Health Committee on April 8th, 2008

[Patrick Orr]

I apologize for any misapprehension. I believe it is well known what drugs are on the market. I didn't mean to imply that no one knows what drugs are on the market. There could be illegal drugs on the market, but generally speaking, it's well known what drugs are on the market. What isn't necessarily known are the effects of those drugs.

Your second question was on who's responsible for the effects of the drug once it's on the market. Health Canada says it's not responsible; that's its departmental position. Industry has been trying to avoid responsibility. We're getting cases in the States--this doesn't affect Canada directly--where pharmaceutical companies that are mostly based in the States are arguing that once FDA approval is given, they are not responsible for manufacturers' liability. Even if a bad product gets approval, they're scot-free. They have no liability for the product, even for adverse reports. So industry is trying to get out of responsibility.

In my own dealings in litigation with Health Canada, their argument is that the physician and the patient are responsible. So it's caveat emptor, buyer beware. The physician is expected to know all the effects of drugs, and if they're bad ones, even unintended ones, the physician is the one at fault.

Thank you.

[Luc Malo, Bloc, Verchères—Les Patriotes, QC]

How do you feel about the suggestion that an independent agency should be responsible for drug surveillance? Could that be the solution?

[Patrick Orr]

That is possibly a solution. It might avoid the problem now, that once Health Canada approves a drug it's very difficult to admit they made a mistake. At least two-thirds of their funding comes from industry, so it's difficult to criticize the people who are paying the budget. So an independent agency might be the solution.

[Luc Malo, Bloc, Verchères—Les Patriotes, QC]

Professor Morgan, you stated in your presentation that voluntary regulation of the industry does not work and that examples can be cited to prove that fact.

Would you elaborate on that statement? In which countries is a voluntary regulatory scheme working, and why is it not working in others?

My next question is similar to the one I put to Mr. Orr earlier. In your opinion, is it not critically important for the industry to ensure that the products it puts on the market are effective, precisely to ensure long-term profitability?

[Dr. Steve Morgan]

I think the key point I would like to make is that you have to design a regulatory framework that compels and actually mandates the manufacturer to complete phase four, or post-marketing trials. The penalty would be withdrawal of the product from the market. Several countries, like the United States, France, the United Kingdom, Australia, and New Zealand, have all tried various regulatory frameworks using various forms of suasion other than strict regulation, to encourage firms to engage in these post-market studies. A significant majority of the studies never get completed.

In New Zealand, they created legislation allowing the medical regulatory agency to commission their own studies of post-market safety and effectiveness for medicines. It commissioned those studies to independent academic groups to ensure they were completed in a public and transparent way.

That appears to be New Zealand's solution to the difficulty of compelling a business to complete a study. In some sense, if the regulatory framework says once it's on the market, it's on the market; it's not in the businesses' interest. That's not to blame firms; that's just the nature of business.

We need to change the regulatory framework to either make regulatory requirements subject to withdrawal or to say that the government will engage in the studies and adequately fund the studies to ensure they're completed.

[Luc Malo, Bloc, Verchères—Les Patriotes, QC]

Earlier on in the consultation process, several witnesses told us that very few adverse effects are reported by doctors.

Why do you think that is the case? In your opinion, what steps could be taken to increase the degree to which adverse effects are reported?

[Dr. Steve Morgan]

That is a major question. How do we increase the degree to which adverse events are reported? Even when you compel a doctor, a pharmacist, or a hospital to report events, systems tend to report, in the best situations, on average about 10% of adverse events. Mechanisms to increase reporting include possibly compelling and making it legislation, but are more likely to be active about it. The notion of having trained personnel dedicated within institutions to track and monitor ADRs is a mechanism that might work. In Canada we might then have a network of hospitals across the country in which, at least in the emergency room, there was a trained pharmacist whose responsibility was really to look for adverse events. That's one way to dramatically increase the sensitivity with which we collect this information.

Dr. Carleton's network effectively does that within children's hospitals.

There are other mechanisms. Mary Wiktorowicz, who is speaking next week, can tell you about international experience with that.

[The Chair, Conservative, Joy Smith]

Thank you, Dr. Morgan.

We'll now hear from Madam Wasylycia-Leis.

[Judy Wasylycia-Leis, NDP, Winnipeg North, MB]

Thank you, Madam Chairperson, and thanks to all of you for your excellent presentations.

Patrick, you are right. The government has just tabled two new pieces of legislation that clearly impact on our deliberations today. One is An Act to amend the Food and Drugs Act and to make consequential amendments to other Acts. The second is An Act respecting the safety of consumer products. It will be important for us to hear your reactions to these bills, because that clearly has an impact on anything to do with post-market surveillance. I'm wondering if I can maybe ask all of you, for the benefit of our study on post-market surveillance, if you would be willing to give us a written critique of these two bills from the point of view of this committee's study so that it might enhance our work and our final report. Would all of you be willing to do that?

I have a couple of copies of each of them with me now, so at the end I could leave them with you.

I am concerned that under the guise of modernization we are actually witnessing a legislative approach that might weaken the capacity of government to ensure drugs, foods, and consumer products are put on the market after all precaution has been taken. I'm worried about that because of the focus on progressive licensing. There are pros and cons, but I'd like to ask you what we should look for in terms of this bill to ensure that any focus on progressive licensing doesn't mean we are lowering the bar—as you, Steve and Patrick, said—in terms of what is acceptable, what can be allowed on the market. What should we look for in that regard?

Second, could you tell me just what this might mean? There is a huge set of “whereases” in this bill:

Whereas the Parliament of Canada recognizes that a lack of full scientific certainty is not to be used as a reason for postponing measures that prevent adverse effects on human health if those affects could be serious or irreversible

I am wondering if all three of you could give me a bit of a perspective on that end of the question of progressive licensing in this whole context of what we know has been happening in the department.

Does anybody want to start?

[Dr. Andreas Laupacis]

Sure. I address that a bit in my remarks. I think, again, like anything in life, one is balancing two risks and harms. My view would be that right now the kinds of studies that industry has to come in with to have their drugs licensed are sort of a minimal standard in most times.

Mr. Orr mentioned Trasylol, which is a drug to prevent bleeding in people with bypass surgery. I actually chaired the committee that suggested that the study that looked at Trasylol should stop, because it looked as if it was killing people, compared to the comparative drug. It's a good example, actually, because nobody was saying that Trasylol wasn't effective. There was actually very good evidence that it decreases the risk of bleeding. That's quite clear. The problem was that nobody did the big enough study for long enough to see what its effect upon mortality was, so industry was able to get Trasylol funded because it clearly was....

I slightly disagree with Mr. Orr. I think it's a big exaggerating to give you the sense that we don't know the benefits or the effects of most drugs. I think we do, but often it's these surrogate markers. It's great to know whether it decreases the risk of bleeding, but you sure want to know whether it's increasing the risk of death.

So obviously the down side.... I think I would be looking very carefully to make sure there isn't any marked decrease in the quality of the randomized trials that are required now, which I think is an absolute minimum. There might be some instances of terminal cancer or whatever, where you might be able to make that case, but I'd like to see those specified.

Let me just make one other comment and then I'll stop. That Trasylol study was actually funded by the Canadian Institutes of Health Research, because it was precisely the kind of head-to-head trial that Steve had mentioned drug companies were not interested in doing. They were not interested in comparing their active drug with the competitor's active drug. The Canadian Institutes of Health Research funded a total of seven randomized trials last year--seven. I don't know what they were about, but I'm sure all seven weren't about drugs.

I think one thing this committee should look at is increasing somehow—in our network we were suggesting we would fund more trials—or encouraging or providing the funds to the CIHR to be able to fund more of the kinds of studies you folks and Canadians would want to know about, which would provide the information about the benefits and risks of drugs.

[Judy Wasylycia-Leis, NDP, Winnipeg North, MB]

How much time is left? I want to make sure both Steve and Patrick—

[The Chair, Conservative, Joy Smith]

Two minutes.

[Judy Wasylycia-Leis, NDP, Winnipeg North, MB]

Can each of you take a minute at least on this?

[Dr. Steve Morgan]

Very quickly, I think I would look to ensure that the progressive licences are only used in circumstances that are extremely dire, in which there are compelling and compassionate grounds for making access to a medicine early, on the basis of compassion. Making access to yet another drug to manage cholesterol faster in the name of access to medicines is not necessarily, in my opinion, appropriate. So I would look for that, and I would also look for the double edge of this rapid access, which would be to ensure a greater amount of transparency.

If a manufacturer is going to bring a product to market with little or no evidence of effectiveness, whatever evidence it has, no matter how commercially important it is to the manufacturer, it is asking Canadians to effectively be guinea pigs, and therefore Canadians ought to have access to every piece of trial data that was submitted to Health Canada.

[Judy Wasylycia-Leis, NDP, Winnipeg North, MB]

Thank you.

Patrick.

[Patrick Orr]

Thank you.

First, the portion of the bill you mentioned, read out, I believe is the precautionary principle, which was developed at the Rio summit on environmental matters, which is that you must take action even in cases of scientific uncertainty. I believe that's what it is, which is a positive thing.

[Judy Wasylycia-Leis, NDP, Winnipeg North, MB]

Okay. I think you could read it almost both ways, but that's good to hear.

[Patrick Orr]

I'll be optimistic on that interpretation.

[Judy Wasylycia-Leis, NDP, Winnipeg North, MB]

Okay.

[Patrick Orr]

The other thing the bill should deal with, I believe, is—besides the things I mentioned—basically mandatory compulsory obligations on either officials or industry to do something. So rather than just having everything discretionary—people may do this or may do that—things should actually be required to be done in certain events, and of course the triggering events will be the threshold. Is it very, very high—serious injury or death—or is it a lower threshold?

[The Chair, Conservative, Joy Smith]

Thank you, Mr. Orr.

Ms. Davidson.

[Patricia Davidson, Conservative, Sarnia—Lambton, ON]

Thank you very much, Madam Chair, and thank you very much to our presenters. We certainly have heard interesting presentations this morning.

I'd like to start with Mr. Orr, if I could, please. I think you said, if I understood you correctly, that we need to have a legislative requirement to do post-market surveillance, that what's in place today is not adequate, and that the legislative requirement should be there to do it properly and to get the best results that we need.

So I've got two or three things I want to ask you. That is one. Then you also talked about a definition of an adverse reaction that I believe is different from the definition we have today, although I'm not so sure there's a very specific definition today that is used by everyone. So maybe you could go over the four or five points that need to be in that definition.

Also, you talked about the medical devices, and you specifically mentioned the TMJ issues. In your opinion, what specific changes to the medical devices regulatory framework would strengthen post-market surveillance in Canada? Could you comment on those three things, please?

[Patrick Orr]

Thank you.

The first question was on the legislative requirement. Perhaps it's because I'm a legislative lawyer and I draft legislation, but I believe legislation is generally a good thing, and yes, it's true, I believe for effective post-market surveillance you need legislation. I believe the government has accepted that principle in introducing today a bill on that very subject. I don't believe I have any disagreement with the government on this point.

Your second point was on the definition of an adverse reaction. There is, in the food and drug regulations, a definition of serious adverse drug reaction. I have that in my notes. The definition I gave is what I would call the ideal definition. I did not make this up myself; I got it from Dr. Ed Napke, who designed the first adverse reporting system in Canada. It included everything--devices, drugs, poison. So this is his recommendation that I'm passing along.

The first is that the drug, including its inactive ingredients, or the “incipients”, as they're often called, itself causes no therapeutic benefit, or no diagnostic benefit, no prophylactic benefit--no effect at all--or no injury, not just an injury that isn't known to be a side effect. So if bleeding ulcers are expected and people start having bleeding ulcers, that should also be reported. You're deemed to have assumed the risk, but I think most people in their heart don't believe they're going to get the side effect. It will be someone else, not them, who will be among the 10% who get the side effect.

Finally, with regard to the medical device regulations, I actually did prepare for that in case the question came up. These are even worse than for drugs. There's mandatory reporting only if there's death or serious deterioration of health. And that's only inside Canada. If these devices are causing death outside Canada, there's no obligation to report unless someone has started taking corrective action. If the industry is not correcting it, and no one else is aware of it or no one has taken steps, there is no obligation to even report deaths from medical devices outside Canada; it's only inside Canada.

[Patricia Davidson, Conservative, Sarnia—Lambton, ON]

Thank you.

Dr. Morgan, I would like to ask you a couple of questions. From your perspective, what is working well within the post-market surveillance system? What should we be focusing on for improvement? Perhaps you can start with that one.

[Dr. Steve Morgan]

Thanks.

I'm a fan of the line of appreciative inquiry: begin with what you do well and build on that. I think there are a few things. An example would be Isis, a Toronto institute where they're doing excellent evaluation or pharmaco-vigilance work by choosing drugs or drug categories that seem to have a potential risk or a potential benefit that needs to be measured or better determined in the real world environment.

I think we have research centres that are doing excellent work of that nature. I think we are developing databases in Canada. British Columbia has some of the best in the world. I think other provinces are on board in expanding their ability to collect and link data that would be necessary for this kind of research. When Quebec and Ontario are fully developed in that area, it will create the world's largest database for monitoring the safety and effectiveness of medicines.

I also think we've done a lot of work about how to prioritize, how to consult, how to conceive of using our interprovincial network of centres and researchers and policy-makers to create, if you will, a laboratory in Canada. We have a very culturally diverse population, which means that we can actually do research on the effect of medicines on specific populations. We also have effectively 13 different schemes for what's reimbursed and what's not. That creates a natural laboratory to determine what works and what doesn't in terms of policy. It also helps to possibly determine which drugs are effective and which are not, based on differential availability in Canada.

So a few things are done well, as are many more, I'm sure. I think we're off to a good start. What we don't have is this coordinating mechanism and an infrastructure, if you will, to make sure this is done in a way that's deliberate, planned, and sustained, as is necessary to really inform regulatory practice as well as, frankly, a provincial reimbursement policy, which could well be informed by this kind of evidence.